The present invention relates to a novel nonvented gravity fed exponential mixing and delivery system and apparatus useful for the administration of a drug in a precalculated manner to give constant therapeutic blood plasma levels in the patient.
The prior art discloses gravity fed intravenous (IV) administration systems for controlling the quantity of a single fluid to be delivered to the patient and/or to provide a controlled rate of flow thereof, as shown in U.S. Pat. Nos. 2,827,081, No. 2,853,069, No. 4,000,738, and No. 4,136,693. However, none of aforesaid systems include, nor make provision for, the mixing of two liquids generally or exponentially.
The prior art also discloses the insertion of mixing devices into an IV system for mixing two liquids or a solid and a liquid, to form a single solution of equal concentration during the total infusion period, as disclosed in U.S. Pat. No. 3,670,728 wherein two different liquids are packaged in a dual chamber flask separated by a septum capable of being upset to enable mixing of the two liquids, assisted by inletting air at the bottom of the flask and initiated by a pumping device for hand operation. U.S. Pat. No. 4,392,850 discloses an in-line transfer container containing a solid material to be intermixed in an IV solution, and serving as a mixing container, disposed below the IV solution container and provided with pierceable diaphragms at opposing ends to provide a fluid passageway for the incoming IV solution into the mixing container, wherein the flexible end wall thereof, is pumped to assist in the intermixing of the IV solution with the material in the mixing chamber, and subsequently piercing the opposing diaphragm to permit the fluid mixture to flow through the IV tubing to the patient. The use of this device involves multiple steps, requiring human intervention, and an excessive amount of time which may be life threatening in an emergency situation. U.S. Pat. No. 4,410,321 discloses a closed drug delivery system for separately storing and selectively mixing two components such as a drug and diluent under sterile conditions, comprising a compressible chamber containing a sterile liquid, a drug vial and a pierceable access means therebetween to create a pathway for the drug to flow into the compressible chamber which is positioned by hand manipulation to facilitate mixing of the drug and the liquid into a solution of uniform concentration for administration to the patient. However, none of aforesaid mixing systems effect exponential mixing nor are they gravity fed.
U.S. Pat. No. 4,424,056 discloses a parenteral administration system of delivering a fluid through a primary path, and a mixture of fluid and medicinal agent through a parallel path wherein the fluid passes through a formulation chamber containing an agent which dissolves in said fluid, and flows into the primary path for delivery to the patient at a controlled rate. The mixing that occurs in the formulation chamber is not exponential mixing.
None of aforesaid patents relate to the particular problems associated with the administration of certain drugs which require a constant plasma drug concentration, small variations thereof being either therapeutically ineffective or toxic. In either case, the results may be serious. This is particularly applicable in the intravenous administration of antiarrhythmic drugs such as lidocaine and other drugs that require a constant plasma drug concentration. Prior art methods used a loading dose and a maintenance infusion at a constant rate. This has been found to be suboptimal due to the production of wide variations in plasma drug concentrations early in therapy. Another prior art method used a series of precisely timed infusion rate changes, which merely minimized said variability and had the additional disadvantage of requiring human intervention at said timed intervals, which detracts from the ability to devote maximum attention to critical patients.
The best method heretofore utilized is the administration of an initial loading dose and an exponentially decreasing infusion rate obtained by approximation using mechanical constant rate infusion pumps and stepped decreases in the delivery rate. This method has the disadvantage of requiring frequent human intervention which is undesirable in a clinical setting.
An improvement on the above exponential infusion rate method utilizing a constant flow rate, is disclosed in Annals of Internal Medicine, 1984, Vol. 100, pp. 25-28, wherein a diluting solution of the drug, e.g. lidocaine, is mechanically pumped from a vented IV set into the base of a 20 ml multiple dose vial containing 1% lidocaine at a rate of 1 ml/min, said entering solution displacing solution at an equal rate from a needle inserted at the base of said vial. The resulting infusion concentration which decreases exponentially, is delivered to the patient. This apparatus has the disadvantage of requiring expensive equipment as well as cumbersome, such as a pump, which requires human intervention to start and stop said pump. There is a possibility of mechanical malfunction of the pump which would interfere with the drug infusion into the patient and its concommitant adverse effects such as insufficient drug therapy or toxic side effects due to increased drug infusion. The use of vented equipment is open to contamination from the air and a potential break in the sterility of the drug infusion.
None of the above cited art discloses a gravity fed, non-vented exponential mixing and delivery system and apparatus for the administration of a drug in a precalculated manner to give constant therapeutic blood plasma levels in the recipient.